Corrigendum to “Activation of Melanocortin Receptors MC1 and MC5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy”

We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12–16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors,Mc1randMc5r. The intravitreal injection (5 μL) of the selective MC1small molecule agonist BMS-470539 (33 μmol) and the MC5peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1β, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5and MC1antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4agonist/antagonists resulted to be inactive with respect to all parameters under assessment.

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Role of Oxidative Stress in Diabetic Retinopathy and the Beneficial Effects of Flavonoids

Current Pharmaceutical Design ◽

10.2174/1381612824666180515151043 ◽

2018 ◽

Vol 24 (19) ◽

pp. 2180-2187 ◽

Cited By ~ 7

Author(s):

Mohammad Shamsul Ola ◽

Dalia Al-Dosari ◽

Abdullah S. Alhomida

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Experimental Studies ◽

Developed Countries ◽

Retinal Damage ◽

Beneficial Effects ◽

Diabetic Retina ◽

Retinal Pathology ◽

Dietary Flavonoids

Diabetic Retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious change through dysregulation of cellular physiology that damages both neuronal and vascular cells. In this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contribute to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by our group and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the beneficial effects of the six major flavonoid families, such as flavanones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flavanoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in diabetes. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR.

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The vasomotor function of endothelium and elasticity of the arterial wall in the patients with type 1 diabetes mellitus at different stages of diabetic retinopathy

Problems of Endocrinology ◽

10.14341/probl201258422-26 ◽

2012 ◽

Vol 58 (4) ◽

pp. 22-26

Author(s):

E P Kosobian ◽

I Ia Iarek-Martynova ◽

A S Parfenov ◽

M V Shestakova

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Diabetic Retinopathy ◽

Type 1 Diabetes Mellitus ◽

Healthy Subjects ◽

Reactive Hyperemia ◽

Signal Amplitude ◽

Stiffness Index ◽

Retinal Damage

The objective of the present work was to estimate the degree of rigidity of the vascular wall and endothelial function in the patients with type 1 diabetes mellitus at different stages of diabetic retinopathy and in its absence. The study included 118 patients at the age from 18 to 40 years presenting with type 1 diabetes mellitus more than 5 years in duration. The patients were divided into several groups based on the stage of diabetic retinopathy (DR). The control group was comprised of 23 healthy subjects. The contour pulsed wave analysis and the reactive hyperemia test were performed with the use of an Angioscan device. All the patients gave the informed consent to participate in the study. The aortic stiffness index (SI) in all groups of the patents with DM1 and DR was higher than in the healthy subjects. However, the SI values remained normal in the DM1 patients without DR. An increase of SI values was unrelated to the presence of arterial hypertension. The analysis of RI values revealed no statistically significant differences between the groups. The reactive hyperemia test has demonstrated a decrease in the increment of the post-occlusive signal amplitude in a large number of patients suggesting endothelial dysfunction. This decrease was apparent even in the patients exhibiting no signs of retinal damage. However, despite the overall decrease of this parameter, many patients showed its paradoxically high values that probably reflected the elevated baseline level of nitric oxide. The increase of aortic stiffness index with the progression of diabetic retinopathy may be used as an early marker of macrovascular complications even in the patients without arterial hypertension. The lowering of the increment of the post-occlusive signal amplitude in the patients having no signs of retinal damage is indicative of endothelial dysfunction as early as the preclinical stage of DR development. The paradoxically high increment of the signal amplitude is supposed to be associated with the elevation of the baseline level of nitric oxide that in its turn reflects the severity of inflammation and is a factor of high risk of progression of angiopathies.

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Oxidative Stress in Diabetic Retinopathy

Antioxidants ◽

10.3390/antiox10010050 ◽

2021 ◽

Vol 10 (1) ◽

pp. 50

Author(s):

Ángel L. Ortega

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Vascular Complication ◽

Retinal Damage

Diabetic Retinopathy (DR) is a progressive asymptomatic neuro-vascular complication of diabetes that triggers irreversible retinal damage [...]

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Diabetic Retinopathy. Morphofunctional State of the Retina in Pancreas Recipients

Ophthalmology in Russia ◽

10.18008/1816-5095-2021-3-459-469 ◽

2021 ◽

Vol 18 (3) ◽

pp. 459-469

Author(s):

I. V. Vorobyeva ◽

L. K. Moshetova ◽

A. V. Pinchuk ◽

E. V. Bulava ◽

K. E. Lazareva ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Pancreas Transplantation ◽

Patient Management ◽

Molecular Mechanisms ◽

Vision Loss ◽

Retinal Damage ◽

Common Complication ◽

Immunological Markers

Diabetes mellitus (DM) is one of the most common and rapidly progressing diseases worldwide. Diabetic retinopathy (DR) is a common complication of diabetes and the main cause of vision loss in middle-aged and elderly people. The development and progression of DR is closely related to the duration of diabetes, hyperglycemia, and arterial hypertension. There is growing evidence that inflammation is one of the key links in the pathogenesis of diabetic retinal damage, but the exact molecular mechanisms remain to be known. Pancreas transplantation (PT) is currently the only effective treatment for diabetes that restores normal physiological glucose metabolism. Due to the limited number of PT surgeries associated with the severity of intra- and postoperative complications and the acute issue of organ donation, studies on the assessment of DR after PT are few and contradictory. There is a need for further studies of the DR state after PT with the study of the influence of risk factors, determination of the level of immunological markers and the use of modern instrumental research methods to create effective patient management regimens in the postoperative period.

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Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.718902 ◽

2021 ◽

Vol 12 ◽

Author(s):

Carlo Gesualdo ◽

Cornel Balta ◽

Chiara Bianca Maria Platania ◽

Maria Consiglia Trotta ◽

Hildegard Herman ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Diabetic Retinopathy ◽

Growth Factor ◽

Drug Repurposing ◽

Melanocortin Receptors ◽

Control Group ◽

Vascular Endothelial ◽

Diabetic Mice ◽

Dynamic Simulations ◽

Endothelial Growth Factor

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.

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Role of MMP-9 in Diabetic Retinopathy

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i6-s.4635 ◽

2020 ◽

Vol 10 (6-s) ◽

pp. 122-124

Author(s):

Ekawaty Suryani Mastari ◽

Sry Suryani Widjaja ◽

Yahwardiah Siregar ◽

Mutiara Indah Sari

Keyword(s):

Diabetic Retinopathy ◽

Cell Adhesion Molecules ◽

Diabetic Patients ◽

Retinal Damage ◽

Complex Mechanism ◽

Keywords Diabetic Retinopathy ◽

Blood Retinal Barrier ◽

Angiogenesis Process ◽

Permeability Damage

Diabetic retinopathy is a common neurovascular complication of diabetic that strike a third of diabetic patients worldwide. Complex mechanism of biomolecules including enzyme and cytokines is related to oxidative stress of constant hyperglycaemia. Vascular permeability damage resulting from endothelial leakage and apoptosis of Muller cell is the main mechanism of retinal damage. MMPs as endopeptidases have an important role in angiogenesis process of retinopathy by working with various molecules of growth factors, chemokines, cytokines and cell adhesion molecules. MMP-9 has been widely shown to be associated with inflammation, blood-retinal barrier disruption, cell apoptosis and neovascularization in the diabetic retinopathy pathomechanism. Keywords: Diabetic retinopathy; MMP; MMP-9; Blood-retinal barrier

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Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

BioMed Research International ◽

10.1155/2015/364924 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 10

Author(s):

Andrea Matteucci ◽

Monica Varano ◽

Cinzia Mallozzi ◽

Lucia Gaddini ◽

Marika Villa ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Animal Models ◽

Significant Contribution ◽

Therapeutic Strategies ◽

Experimental Models ◽

Retinal Cell ◽

Retinal Damage ◽

Retinal Cultures

Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conductedin vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabeticmilieuon retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight.

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